A Novel Dipeptide Ligand of TSPO

Dokl Biochem Biophys. 2019 May;484(1):17-20. doi: 10.1134/S1607672919010046. Epub 2019 Apr 22.

Abstract

On the basis of the first dipeptide ligand of TSPO, N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide (GD-23), which was obtained by us earlier, we synthesized a new dipeptide, N-phenylpropionyl-L-tryptophanyl-L-leucine amide (GD-102). GD-102 exhibited anxiolytic activity in the open field test in BALB/c mice and in the elevated plus maze test in ICR mice. The minimum effective dose of GD-102 was one order of magnitude lower than that of GD-23. Compound PK11195, a selective antagonist of TSPO, completely blocked the anxiolytic activity of GD-102, which testified to the involvement of TSPO in the realization of the anxiolytic effect of GD-102. The results were confirmed by molecular docking data.

MeSH terms

  • Anti-Anxiety Agents / chemistry*
  • Anti-Anxiety Agents / pharmacology
  • Dipeptides / chemistry*
  • Dipeptides / pharmacology
  • Humans
  • Molecular Docking Simulation*
  • Receptors, GABA / chemistry*
  • Receptors, GABA / metabolism

Substances

  • Anti-Anxiety Agents
  • Dipeptides
  • Receptors, GABA
  • TSPO protein, human